FOLFOXIRI and Panitumumab in mCRC Treatment – Improvement in Treatment Response and Metastasis Resectability
For patients with metastatic colorectal cancer (mCRC) who are able to undergo intensive treatment, the FOLFOX (5-fluorouracil/leucovorin, oxaliplatin) or FOLFIRI (5-fluorouracil/leucovorin, irinotecan) regimens combined with monoclonal antibodies represent the standard first-line treatment. The FOLFOXIRI regimen, which is another option, was developed to further enhance the efficacy of chemotherapy. The German oncologists' VOLFI study investigated the effectiveness of combining targeted therapy and triplet chemotherapy compared to chemotherapy alone in previously untreated patients with mCRC without RAS oncogene mutation.
Study Methodology
The primary aim of the randomized, open-label phase II study was the objective response rate (ORR) evaluated following RECIST criteria. The researchers predefined that treatment in the experimental arm (modified FOLFOXIRI [mFOLFOXIRI] and panitumumab) would be considered effective if ORR reached ≥ 75%, and ineffective if it was ≤ 60%, which was the historical ORR estimate for FOLFOXIRI. Results from the experimental arm were compared with the control arm, which included patients treated only with the FOLFOXIRI chemotherapy regimen. Secondary objectives included secondary resectability rate, treatment toxicity, progression-free survival (PFS), and overall survival (OS).
Results
A total of 63 patients were randomized to the experimental arm, and 33 to the control arm. The ORR values for the mFOLFOXIRI and panitumumab combination exceeded 75% and were higher compared to FOLFOXIRI (87.3% vs. 60.6%; odds ratio [OR] 4.469; 95% confidence interval [CI] 1.61–12.38; p = 0.004).
The secondary resectability rate nearly tripled with the addition of panitumumab (33.3% vs. 12.1%; p = 0.02). PFS was similar in both arms, with OS showing a slight but not statistically significant trend towards improvement in the mFOLFOXIRI and panitumumab group (hazard ratio [HR] 0.67; 95% CI 0.41–1.11; p = 0.12).
Regarding toxicity, the mFOLFOXIRI and panitumumab regimen appeared riskier, with grade 3 and 4 adverse events occurring in 81.3% of patients compared to 66.7% in the control arm. The most common adverse events were diarrhea and skin issues typical for anti-EGFR therapy. One treatment-related death was recorded in the control arm (caused by peripheral embolization).
Conclusion
Adding panitumumab to mFOLFOXIRI improved the objective response rate and metastasis resectability in mCRC patients, presenting a therapeutic alternative for selected patients in good condition who need highly effective first-line treatment. Further studies with larger patient numbers should focus on whether adding panitumumab to FOLFOXIRI also extends patient survival.
(mir)
Source: Modest D. P., Martens U. M., Riera-Knorrenschild J. et al. FOLFOXIRI plus panitumumab as first-line treatment of RAS wild-type metastatic colorectal cancer: the randomized, open-label, phase II VOLFI Study (AIO KRK0109). J Clin Oncol 2019; 37 (35): 3401–3411, doi: 10.1200/JCO.19.01340.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
